Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report

Çağatay, Atahan; Öncü, Serkan; Çalangu, Semra; Yıldırmak, Taner; Özsüt, Halit; Eraksoy, Haluk

doi:10.1186/1471-2334-1-22

Cited by 52 publications

(23 citation statements)

References 14 publications

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“…For example, in contrast to US$5 per day for a 1-mg/kg daily dose of amphotericin B deoxycholate, 5 to 15 mg/kg of lipid-based amphotericins can cost between US$500 and US$3,000 per day (142). Nevertheless, several case reports and case series of patients with mucormycosis have documented successful outcomes with either liposomal amphotericin B or amphotericin B lipid complex (21,38,170,173).…”

Section: Antifungal Therapymentioning

confidence: 99%

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005

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Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement

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Section: Antifungal Therapymentioning

confidence: 99%

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005

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“…ABLC was as effective as LAmB in neutropenic but not DKA mice. Low-dose ABLC was less effective than LAmB at reducing brain fungal burdens in both models.Case reports and case series have documented successful outcomes after the treatment of zygomycosis with either liposomal amphotericin B (LAmB) or an amphotericin B lipid complex (ABLC) (1,4,14,15). To date, there have been no head-to-head preclinical or clinical studies comparing the efficacy of LAmB to that of ABLC for zygomycosis.…”

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confidence: 99%

Comparison of Lipid Amphotericin B Preparations in Treating Murine Zygomycosis

Ibrahim

Gebremariam

Husseiny

et al. 2008

Antimicrob Agents Chemother

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We compared the efficacies of liposomal amphotericin B (LAmB) and an amphotericin B lipid complex (ABLC) in diabetic ketoacidotic (DKA) or neutropenic mice with disseminated zygomycosis. ABLC was as effective as LAmB in neutropenic but not DKA mice. Low-dose ABLC was less effective than LAmB at reducing brain fungal burdens in both models.Case reports and case series have documented successful outcomes after the treatment of zygomycosis with either liposomal amphotericin B (LAmB) or an amphotericin B lipid complex (ABLC) (1,4,14,15). To date, there have been no head-to-head preclinical or clinical studies comparing the efficacy of LAmB to that of ABLC for zygomycosis. However, relevant to the treatment of central nervous system (CNS) zygomycosis, a previous rabbit study demonstrated that LAmB penetrates the brain parenchyma at levels more than fivefold above those of ABLC (6). In fact, in that study, the levels of ABLC in the brain were less than or equal to the levels of amphotericin B deoxycholate, despite the fact that ABLC was administered at a fivefold-higher dose. Conversely, recent data demonstrated the efficacy of ABLC therapy in treating experimental CNS aspergillosis (3) and rabbit coccidioidal meningitis (2), suggesting the ability of ABLC to penetrate the brainblood barrier. A recent retrospective review of 120 cases of zygomycosis in patients with hematological malignancies demonstrated that treatment with LAmB was associated with a 67% survival rate, compared to a 39% survival rate when patients were treated with amphotericin B deoxycholate (P ϭ 0.02; 2 test) (5). No comparable data set from a review of the effect of ABLC in this setting has been published. Therefore, we sought to compare the efficacy of LAmB to that of ABLC in treating zygomycosis.(This work was presented in part at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 17 to 20 September 2007 [12].)To define the relative efficacies of ABLC and LAmB against zygomycosis, we utilized our diabetic ketoacidotic (DKA) mouse model of disseminated zygomycosis, in which heavy infection occurs both systemically and specifically in the CNS (7-10). BALB/c male mice (20 to 23 g) were rendered diabetic with a single intraperitoneal injection of 210 mg of streptozotocin/kg of body weight in 0.2 ml of citrate buffer 10 days prior to fungal challenge, as we have previously described (7-10). Glycosuria and ketonuria were confirmed in all mice 7 to 10 days after streptozotocin treatment. Diabetic mice were infected via the tail vein with Rhizopus oryzae 99-880, a clinical brain isolate known to be virulent and tropic toward the brain in our model and susceptible to amphotericin B (MIC ϭ 0.25 g/ml) (8). LAmB or ABLC (7.5 or 15 mg/kg/day) was diluted in 5% dextrose water and administered intravenously (i.v.) in 0.2 ml for 4 days starting 24 h after infection. These doses were selected based on results from prior studies demonstrating

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“…The lipid formulations of AmB are significantly less nephrotoxic than AmB and can be administered at higher doses. Several case reports of patients with zygomycosis document successful treatment with LAmB up to 15 mg/kg/day (3,6,14). Although there is a developing consensus that high doses of lipid formulation AmB should be the initial antifungal therapy of choice for all patients with zygomycosis (9), until now there have been no data available to define the relative efficacies of the lipid formulations of AmB versus AmB for zygomycosis.…”

mentioning

confidence: 99%

Liposomal Amphotericin B, and Not Amphotericin B Deoxycholate, Improves Survival of Diabetic Mice Infected with Rhizopus oryzae

Ibrahim

Avanessian

Spellberg

et al. 2003

Antimicrob Agents Chemother

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The efficacies of liposomal amphotericin B (LAmB) and amphotericin B deoxycholate (AmB) were compared in a diabetic murine model of hematogenously disseminated Rhizopus oryzae infection. At 7.5 mg/kg of body weight twice a day (b.i.d.), LAmB significantly improved overall survival compared to the rates of survival in both untreated control mice (P ‫؍‬ 0.001) and mice treated with 0.5 mg of AmB per kg b.i.d. (P ‫؍‬ 0.047). These data indicate that high-dose LAmB is more effective than AmB in treating murine disseminated zygomycosis.Zygomycosis is a frequently fatal infection that occurs in patients with elevated available levels of iron in serum, such as those treated with deferoxamine, or in patients immunocompromised by diabetic ketoacidosis, organ transplantation, or neutropenia (2, 12). The therapy for invasive zygomycosis includes reversal of the underlying predisposing factors, emergent surgical debridement, and antifungal chemotherapy (5,10,12). Although prospective clinical studies are lacking, amphotericin B deoxycholate (AmB) remains the antifungal therapy of choice for invasive zygomycosis (5, 12), largely because of a historical lack of alternative cidal therapies. Because the fungus is relatively resistant to AmB, high doses are required, frequently resulting in nephrotoxicity and other adverse effects (12). Even when surgical debridement is combined with highdose AmB, the mortality associated with zygomycosis exceeds 50% (12). This mortality rate approaches 100% in patients with disseminated zygomycosis, possibly because surgery to remove the infected foci is not feasible (2). These data emphasize the critical need for more effective antifungal chemotherapy for this lethal infection.The lipid formulations of AmB allow the administration of higher drug doses due to their limited toxicities (1, 4). Scattered case reports have demonstrated successful outcome in patients with zygomycosis treated with lipid-associated AmB (7,8). Since diabetic ketoacidosis represents a major risk factor for the development of zygomycosis infection (5, 12), we used a diabetic mouse model to compare the efficacy of high doses of liposomal AmB (LAmB) against that of AmB in treating hematogenously disseminated zygomycosis caused by Rhizopus oryzae, the most common etiologic pathogen of zygomycosis (11).(This work was presented in part at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Calif., 27 to 30 September 2002.)R. oryzae 99-880 was obtained from the Fungus Testing Laboratory, University of Texas Health Science Center, San Antonio. This strain was isolated from a brain abscess of a diabetic patient with rhinocerebral zygomycosis. Spores were collected by flooding potato dextrose agar plates (PDA) with 7 ml of endotoxin-free phosphate-buffered saline (PBS) containing 0.01% Tween 80 and gently scrapping the aerial mycelium.Male BALB/c mice (Ն24 g) were rendered diabetic with a single intraperitoneal (i.p.) injection of 210 mg of streptozocin per kg of body weight in 0.2 ml of ice-cold...

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Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report

Cited by 52 publications

References 14 publications

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

Comparison of Lipid Amphotericin B Preparations in Treating Murine Zygomycosis

Liposomal Amphotericin B, and Not Amphotericin B Deoxycholate, Improves Survival of Diabetic Mice Infected with Rhizopus oryzae

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